The specimens measure approximately 1 to 3.5 mm in length and have 1 to 29 pairs of somites.

The head and tail folds move the attachment of the amnion to the ventral side of the head and tail regions, respectively. The lateral body folds move the amnion attachment to the ventrolateral surface in the midportion of the embryo.

The head region is elevated above the yolk sac by the large pericardial sac, the midportion lies upon the yolk sac and the caudal region is curved toward the yolk sac.

The embryo possesses somites, which are apparent through the ectoderm.

The neural tube develops from the neural plate and remains open at each end for 2 to 4 days.

There may be two dorsolateral enlargements in the head region, the trigeminal and otic prominences, separated by the preotic sulcus. The trigeminal prominence is continuous ventrally with the broad first branchial arch that extends to the pericardial sac. The otic prominence is continuous ventrally with an area that will soon become the second branchial arch.

ECTODERM

NERVOUS SYSTEM

The neural plate is transformed into the neural tube as a result of the neural folds joining in the midline dorsally. The rostral and caudal openings of the tube are called neuropores. The rostral neuropore closes between 18 and 20 somites. The caudal neuropore closes at 25 somites.

Brain

Three brain subdivisions are present in the cranial portion of the tube and are named, from cranial to caudal, the prosencephalon, mesencephalon and rhombencephalon. The boundary between the pros- and mesencephalon is demarcated by a ventral bend, called the cephalic flexure. An external groove and a prominent swelling on the medial surface of the neural plate may also demarcate the boundary. The boundary between the mes- and rhombencephalon is distinguished by a groove on the medial and lateral surfaces of the neural plate or tube.

ProsencephalonThe medial surface possesses a broad, shallow depression, called the optic groove, where the optic cup will form by evagination after closure of the neural tube. This is the first appearance of the eye. The optic chiasmal area is ventral where the two walls come together.

MesencephalonThe mesencephalon is a short segment of the neural plate or tube which bulges internally and externally. Its dorsal portion will form the tectum; its floor and medial wall will give rise to the tegmentum and basis pedunculi area.

RhombencephalonThe rhombencephalon extends from the mesencephalon to the level of somite 4 where it is continuous with the spinal cord segment. It can be subdivided into preotic and postotic portions by placode VIII (otic).

Neural Crests

Collections of cells called neural crests stream from the angle between the neural and superficial ectoderm. The following crests can be recognized during the early part of the fourth week.

Trigeminal CrestThe trigeminal crest is the most rostral of the neural crests and is located at the level of the mesencephalon and the preotic part of the rhombencephalon. Initially, it is the largest of all the neural crests, forming most of the trigeminal prominence. It spreads laterally and is gradually lost in the mesenchyme of the first branchial arch. Its caudal part is closely associated with placode V.

Facioacoustic CrestThe facioacoustic crest is a mass at the level of the otic part of the rhombencephalon and constitutes most of the otic prominence. It blends with mesenchyme of the otic region. Its peripheral portion is associated with placode VII and placode VIII (otic).

Glossopharyngealâ€“Vagal CrestThe glossopharyngealâ€“vagal crest develops midway between the rostral neuropore and somite 1 at the level of the postotic part of the rhombencephalon. Initially it is not well defined and will later become two separate crests. It is closely associated with the deep surface of placode IXâ€“X.

Occipitospinal CrestsOne occipitospinal crest will develop in each body segment between the neural tube and each somite. Initially, it is poorly defined and its cells become scattered among the mesenchymal cells.

ECTODERMAL PLACODES IN THE HEAD REGION

Localized thickenings of the ectoderm called placodes develop on the lateral side of the head in the branchial arch region. They are closely related to the cranial neural crests.

Placode V

Placode V overlies the caudal edge of the trigeminal crest. Its boundaries are poorly defined and it disappears early.

Placode VII

A band of thickened ectoderm represents placode VII and extends from the rostral side of placode VIII (otic) to the first branchial groove. It is also known as the epibranchial placode of the second branchial arch and is associated with the facial part of the facioacoustic crest.

Placode VIII (Otic)

Placode VIII (otic) is the most conspicuous area of ectodermal thickenings and represents the first appearance of the ear. It is located on the summit of the otic prominence and is demarcated caudally by the shallow postotic sulcus. It is associated with the acoustic part of the facioacoustic crest.

Placode IXâ€“X

A tongue shaped area of ectodermal thickening represents placode IX-X and extends caudally from placode VIII to the level of somite 1. Initially, it is associated with the combined glossopharyngeal-vagal crest but soon subdivides into two epibranchial placodes when the IX-X crest becomes distinct and separate.

NOTOCHORD

The notochord develops from the notochordal process and extends in the midline from the cranial end of the foregut to the tail. Initially it is a plate or n shaped and at most levels becomes the dorsal part of the gut lining. It is in contact with the neural tube dorsally and terminates in the head region near the pros- and mesencephalic junction. In the tail region the notochord separates from the gut endoderm, becomes cylindrical and unites with the underside of the neural plate.

ENDODERM

With the development of the head, tail and lateral body folds, the endoderm that previously formed the roof of the yolk sac is molded into blind tubes in the head and tail regions known as the foregut and hindgut, respectively. The intermediate endoderm that remains as the roof of the yolk sac forms the midgut. These three endodermal subdivisions represent the first appearance of the Alimentary and Respiratory Systems.

FOREGUT

The foregut is compressed in the horizontal plane with its lateral portion extending dorsally. Its cranial end terminates blindly at the oropharyngeal membrane. Caudally it opens into the midgut at the anterior (cranial) intestinal portal.

Ventral outpouchings

The buccal pouch is a slight bulge into the oropharyngeal membrane area.

The thyroid diverticulum is the most prominent and deepest outpouching and is located in the midline at the level of the first aortic arches.

A midline trough called the laryngotracheal groove extends caudally from the thyroid diverticulum to the anterior intestinal portal. At its caudal termination the endodermal lining forms a midline bud that represents the unpaired lung primordium (Respiratory System).

Lateral outpouching

The first pharyngeal pouch is a clearly defined bulge extending laterally and dorsally around the side of the dorsal aorta. The closing membrane of the first branchial groove is a small area caudal to pouch 1 where ectoderm and endoderm are in contact.

HINDGUT

Caudally the short, blunt hindgut ends blindly at the cloacal membrane. It opens at its cranial end into the midgut at the posterior (caudal) intestinal portal. The allantoic diverticulum (allantois) arises from the ventral side of the hindgut and passes into the connecting stalk.

MIDGUT

The endoderm of the midgut constitutes the roof of the yolk sac cavity between the cranial and caudal intestinal portals. The septum transversum lies ventral to the cranial intestinal portal where the hepatic diverticulum forms.

MESODERM

Mesoderm is located on each side of the midline and can be subdivided by its location into four portions: head, paraxial, intermediate and lateral.

HEAD MESODERM

Mesenchymal tissue collects throughout the head region beneath the ectoderm. It probably arises from the cranial neural crests and the primitive streak.

PARAXIAL (SOMITIC) MESODERM

The paraxial mesoderm is located on each side of the neural tube where it collects into blocks of epitheloid cells called somites. The somites are triangular shaped on transverse section with dorsal, ventral and medial walls. The epitheloid cells are arranged around a central cavity called the myocoele.

Somites are segmentally arranged with the first pair forming near the cranial end of the embryo in the future occipital region. Segmentation occurs in a craniocaudal sequence with their formation closely trailing the closure of the neural tube.

The somite number is used to determine the relative age of embryos in the somite period. Eventually there are 42 to 44 somite pairs formed (4 occipital, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral and 8 to 10 coccygeal).

By the time the more caudal somites appear, the cranial ones break down as a result of proliferation. The somites will give rise to major components of the Skeletal, Muscular and Integumentary Systems.

INTERMEDIATE MESODERM

The intermediate mesoderm temporarily connects the paraxial with the lateral plate mesoderm.

In the cervical segments the intermediate mesoderm is arranged into a group of cells that produce a nonfunctional, vestigial kidney of lower forms called the pronephros. The pronephros represents the first appearance of the Urogenital System and is a very transitory structure.

During the early part of the fourth week, the pronephros is composed of small, isolated groups of cells called pronephric rudiments at the level of somites 3 to 8. At the level of somites 8 to 10 (C-4 to C-6) the cells form a pronephric ridge. There is no definite evidence of segmentation or lumen formation.

LATERAL (PLATE) MESODERM

Lateral mesoderm lies between the intermediate mesoderm and the extraembryonic mesoblasts at the edge of the embryo.

Intercellular clefts appear in the lateral mesoderm and separate it into an outer layer called somatic mesoderm and an inner layer known as splanchnic mesoderm. As the clefts enlarge and coalesce they produce a cavity between the layers on each side known as the embryonic coelom.

In the midportion of the embryo, the splanchnic mesoderm is continuous laterally with the extraembryonic mesoblasts of the yolk sac. The embryonic coelom communicates laterally with the extraembryonic coelom.

The somatic mesoderm becomes closely associated with the overlying ectoderm and together they form a double layer called the somatopleure. The splanchnic mesoderm is similarly associated with the underlying endoderm and together they form the splanchnopleure. The intervening embryonic coelom is continuous cranially through the pericardioperi-toneal canal (coelomic duct) with the pericardial cavity.

HEART

The heart begins as an endocardial tube that forms in front of the prochordal plate from bilateral angiogenic cell clusters located between the cardiogenic plate and the underlying yolk sac endoderm. The cardiogenic plate is a thickened layer of splanchnic mesoderm that will give rise to the epimyocardium. With the formation of the head fold and the expansion of the prosencephalon, the cardiogenic plate assumes a position ventral to the foregut. The angiogenic cell clusters become a pair of endothelial tubes in the splanchnic mesodermal layer and bulge into the pericardial part of the embryonic coelom. With formation of the lateral body folds, the paired endothelial tubes fuse in the midline producing a single endocardial tube ventral to the foregut.

With continued growth the heart tube assumes an S shape and is suspended from the dorsal wall of the pericardial cavity by a short mesentery called the mesocardium. It is separated from the yolk sac by the septum transversum and is composed of two layers, a thick outer layer called the primitive epimyocardium and a thin inner layer, the primitive endocardium. The two layers are separated by a distinct endomyocardial space, which is filled with cardiac jelly.

The heart tube begins to beat, circulating primitive blood cells through the vessels of the embryo, chorion, connecting stalk and yolk sac. Cranially it is continuous with arteries; caudally it receives the veins.

Three areas can be recognized in the single tube. From cranial to caudal they are as follows.

The aortic sac or roughly ovoid, cranial end of the tube from which the aortic arches arise. It lies mainly in the dorsoventral plane outside the pericardial cavity.

The primitive bulbus cordis or ventral portion curving to the right of the midline is separated from the aortic sac by a slight constriction.

The primitive ventricle is the most prominent dilatation, extending to the left and dorsally at right angles to the primitive bulbus cordis from which it is partially separated by the bulboventricular sulcus.

The single tube bifurcates near the caudal end of the pericardial sac into the two, slightly dilated primitive atria that are in the floor of the cranial intestinal portal. The atria are separated from the ventricle by shallow right and deep left atrioventricular (A-V) sulci. Internally, the single ventricular chamber communicates with both atrial chambers through a single atrioventricular canal.

Each atrium is continuous with a dilated chamber on each side of the cranial intestinal portal called the sinus venosus. Each sinus venosus receives veins from the connecting stalk, chorion and yolk sac.

ARTERIES

The first pair of aortic arches connects the aortic sac with the paired dorsal aortas located on each side, dorsal to the primitive gut. The second pair forms caudal to the first pharyngeal pouch as small, irregular vessels. Cranial to the first arch the dorsal aorta on each side extends toward the pros- and mesencephalon as the internal carotid arteries.

Small sprouts arise from the dorsal aortas along the rhom-bencephalon and between most of the somites. They represent the beginning of dorsal intersegmental arteries.

Each of the dorsal aortas terminates caudally by dividing into many ventral branches that break up into plexuses on the midgut, hindgut and yolk sac. The plexuses connect with the single, large umbilical artery in the connecting stalk that courses to the chorionic villi. The connections on each side will form the right and left umbilical arteries.

VEINS

Tributaries of the large vitelline plexus on the yolk sac come together to form right and left vitelline veins that drain into the sinus venosus on the corresponding side.

Blood from the chorion courses through large spaces in the connecting stalk that join together on each side to form right and left umbilical veins. Each vein passes along the lateral side of the embryo where the amnion attaches and empties into the sinus venosus on that side.

Chains of relatively large capillary blood vessels begin forming the primary head vein on the lateral surface of the neural tube in the head region. These channels will eventually become a part of the cardinal system of veins that drain the embryo.